The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial

Abstract

BackgroundSchizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other.MethodsThis post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern.ResultsWe identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: 1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), 2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and 3) no improvement in either negative or positive symptoms (n = 82, 21%).ConclusionsThis study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.

Re-conceptualizing ASD Within a Dimensional Framework: Positive, Negative, and Cognitive Feature Clusters

“…Rather, this conceptualization has led to improved ability to diagnose and treat, to predict and track course of illness, response to treatment, and functional outcomes in affected patients (Chen et al 2013; Mohr et al 2004), and to begin to understand the universality versus specificity of underlying neural abnormalities and genetic alterations in driving clusters of symptoms within and across individuals (Barch and Ceaser 2012). Positive symptoms are often more acute and transient and respond most reliably to anti-psychotic medications (Angrist et al 1980; Chien and Yip 2013; Leucht et al 2009).…”

The course of negative symptom in first episode psychosis and the relationship with social recovery

“…Moreover, grouping individuals into those with persistent negative symptoms and those without might mask the true complexity of individual variation in negative symptom course. Chen et al (2013) found that variation in negative symptom course in a cohort of schizophrenia patients was best modelled by four distinct trajectory classes, characterised by differing levels of negative symptoms at baseline and a distinctive pattern of longitudinal change. It is not yet known whether multiple negative symptoms trajectories are similarly evident in FEP.…”

Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms

“…More recent literature on response trajectories speaks to the notion of differential treatment response and comes closest to what is observed clinically. [43][44][45][46] At first glance, our proposal to subtype schizophrenia clinically may appear to contradict the recent removal of clinical subtypes in DSM-5 33 ; however, these 2 approaches of clinical subtyping have notable differences. The previous clinical subtypes (paranoid, disorganized, catatonic, undifferentiated, and residual) relied on symptom presentation at a specific point, and symptoms have been known to vary across various phases of the illness; hence it suffered from a lack of diagnostic stability, reliability, and validity.…”